High-protein diet prevents fat mass increase after dieting by counteracting Lactobacillus-enhanced lipid absorption

Dietary restriction is widely used to reduce fat mass and lose weight in individuals with or without obesity; however, weight regain after dieting is still a big challenge, and the underlying mechanisms remain largely elusive. Here we show that refeeding after various types of dieting induces quick fat accumulation in mice and enhanced intestinal lipid absorption contributes to post-dieting fat mass increase. Moreover, refeeding after short-term dietary restriction is accompanied by an increase in intestinal Lactobacillus and its metabolites, which contributes to enhanced intestinal lipid absorption and post-dieting fat mass increase; however, refeeding a high-protein diet after short-term dietary restriction attenuates intestinal lipid absorption and represses fat accumulation by preventing Lactobacillus growth. Our results provide insight into the mechanisms underlying fat mass increase after dieting. We also propose that targeting intestinal Lactobacillus to inhibit intestinal lipid absorption via high-protein diet or antibiotics is likely an effective strategy to prevent obesity after dieting.